Browsing by Author "Safavi-Naeini, M"
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- ItemBENEdiCTE (Boron Enhanced NEutron CapTurE) gamma-ray detection module(IEEE, 2021-10-16) Caracciolo, A; Di Vita, D; Buonanno, L; D'Adda, I; Carminati, M; Charcon, A; Kielly, M; Safavi-Naeini, M; Fiorini, CWe present a gamma-ray detection module for Neutron Capture Enhanced Particle Therapy (NCEPT). The system has been optimised for boron-10 neutron capture agents that can be used for dose enhancement in proton and heavy ion therapy. The goal of the module is to distinguish the photopeak at 478 keV from the prompt-gamma emission resulting from the ion-target nuclear interactions. The module consists of a compact 64-channel module, with a large array of SiPM coupled to a 2" diameter and 2" thickness cylindrical LaBr 3 :Ce scintillator crystal (63 ph/keV conversion efficiency, 16 ns decay time). The electronic front-end ASIC features low-noise processing of photodetector signals, while the pixellated SiPMs detector and individual readout allows for position sensitivity in the crystal. We have characterised the energy resolution of the system experimentally, demonstrating an excellent energy resolution (3.27% at 662 keV), together with the capability of the FPGA-based DAQ integrated in the module to deploy an external synchronization signal to the ion beam bunches, in order to generate anti-coincidence windows. This feature provides a mechanism to distinguish and reject scintillation events from prompt gammas, enhancing the signal-to-background ratio of the spectrometer. © 2021 IEEE
- ItemDetection and discrimination of neutron capture events for NCEPT dose quantification(Springer Nature Limited, 2022-04-07) Chacon, A; Kielly, M; Rutherford, H; Franklin, DR; Caracciolo, A; Buonanno, L; D'Adda, I; Rosenfeld, AB; Guatelli, S; Carminati, M; Fiorini, C; Safavi-Naeini, MNeutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific 10B or 157Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for 10B and 157Gd, respectively. A key requirement for NCEPT’s translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated 300×300×300 mm3 cubic PMMA targets were irradiated by 4He or 12C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include 10×10×10 mm3 neutron capture inserts (NCIs) of pure 10B or 157Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated 50×50×50 mm3 ideal detector were recorded. A temporal mask of 50–60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives (RTF) was calculated; for targets with 10B and 157Gd NCIs, the detector materials which resulted in the highest RTF were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the 10B NCI and 1 ms for the 157Gd NCI. © The Authors, Creative Commons Attribution 4.0 International Licence.
- ItemErratum: Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET (2020 Phys. Med. Biol. 65 125006)(IOP Publishing, 2020-11-21) Mohammadi, A; Tashima, H; Iwao, Y; Takyu, S; Akamatsu, G; Kang, HG; Nishikido, F; Yoshida, E; Chacon, A; Safavi-Naeini, M; Parodi, K; Yamaya, TIn heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u−1) and 15O (312 MeV u−1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume. © 2020 Institute of Physics and Engineering in Medicine.
- ItemEvaluation of silicon detectors with integrated JFET for biomedical applications(Institute of Electrical and Electronics Engineers (IEEE), 2009-06) Safavi-Naeini, M; Franklin, DR; Lerch, MLF; Petasecca, M; Pignatel, G; Reinhard, MI; Dalla Betta, GF; Zorzi, N; Rosenfeld, ABThis paper presents initial results from electrical, spectroscopic and ion beam induced charge (IBIC) characterisation of a novel silicon PIN detector, featuring an on-chip n -channel JFET and matched feedback capacitor integrated on its p-side (frontside). This structure reduces electronic noise by minimising stray capacitance and enables highly efficient optical coupling between the detector back-side and scintillator, providing a fill factor of close to 100%. The detector is specifically designed for use in high resolution gamma cameras, where a pixellated scintillator crystal is directly coupled to an array of silicon photodetectors. The on-chip JFET is matched with the photodiode capacitance and forms the input stage of an external charge sensitive preamplifier (CSA). The integrated monolithic feedback capacitor eliminates the need for an external feedback capacitor in the external electronic readout circuit, improving the system performance by eliminating uncontrolled parasitic capacitances. An optimised noise figure of 152 electrons RMS was obtained with a shaping time of 2 mus and a total detector capacitance of 2 pF. The energy resolution obtained at room temperature (2°C) at 27 keV (direct interaction of I-125 gamma rays) was 5.09%, measured at full width at half maximum (FWHM). The effectiveness of the guard ring in minimising the detector leakage current and its influence on the total charge collection volume is clearly demonstrated by the IBIC images. © 2009, Institute of Electrical and Electronics Engineers (IEEE)
- ItemFluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111(John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BHObjectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
- ItemGd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy(Australian National University, 2021-08-24) Middleton, RJ; Howell, NR; Livio, E; Wyatt, NA; Chacon, A; Fraser, BH; Barnes, M; Cameron, M; Rendina, LM; Häusermann, D; Lerch, M; Safavi-Naeini, MHigh-Z elements have been proposed as radiosensitisers in X-ray photon radiotherapy due to their emission of multiple high-LET photo- and Auger electrons following X-ray irradiation. Gadolinium is a particularly attractive candidate radiosensitiser, since it can also be used as an MRI contrast agent. In this study, we report on the efficacy of Gd-triphenylphosphonium salt-DOTA (Gd(III)-TPP-DOTA) for synchrotron microbeam radiation therapy dose enhancement. The compound utilises the mitochondrial targeting moiety triphenylphosphonium (TPP) to accumulate Gd in the inner mitochondrial membrane. Experiments were conducted using the dynamic mode option at hutch 2B of the Imaging and Medical Beamline at the Australian Synchrotron. Human glioblastoma multiforme cells (T98G cell line) were cultured to 80-90% confluence in T12.5 flasks. Approximately 24 hours prior to irradiation, the cultures were either treated with a 500 μM solution of Gd(III)DOTA-TPP or a vehicle control. Spatial dose distribution of synchrotron broad beam (BB) and single/multiple microbeams were measured using a micron-scale X-Tream dosimetry system and Gafchromic films in air and at 2 cm depth in solid water (same depth as the monolayer of cells in T12.5 flasks). A total of 96 flasks were irradiated, with doses of 0, 1, 2, 3, 4, 5, 10 and 16 Gy delivered in valley (MRT) or uniformly (BB). Post irradiation, each flask was re-seeded into 7 x 96 well-plates to perform the resazurin cell proliferation assay up to 7 days after irradiation. Our preliminary analysis indicates that for cells irradiated by 3 Gy of BB or MRT radiation, the addition of Gd(III)DOTA-TPP results in a reduction in viable cell mass by 24.25% and 25.79%, respectively, compared with untreated flasks. © The Authors
- ItemInfluence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET(IOP Publishing, 2020-06-12) Mohammadi, A; Tashima, H; Iwao, Y; Takyu, S; Akamatsu, G; Kang, HG; Nishikido, F; Yoshida, E; Chacon, A; Safavi-Naeini, M; Parodi, K; Yamaya, TIn heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-To-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u-1) and 15O (312 MeV u-1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume. © 2020 Institute of Physics and Engineering in Medicine
- ItemA Monte Carlo model of the Dingo thermal neutron imaging beamline(Springer Nature, 2023-12-01) Jakubowski, K; Charcon, A; Tran, LT; Stopic, A; Garbe, U; Bevitt, JJ; Olsen, SR; Franklin, DR; Rosenfeld, AB; Guatelli, S; Safavi-Naeini, MIn this study, we present a validated Geant4 Monte Carlo simulation model of the Dingo thermal neutron imaging beamline at the Australian Centre for Neutron Scattering. The model, constructed using CAD drawings of the entire beam transport path and shielding structures, is designed to precisely predict the in-beam neutron field at the position at the sample irradiation stage. The model’s performance was assessed by comparing simulation results to various experimental measurements, including planar thermal neutron distribution obtained in-beam using gold foil activation and BC-coated microdosimeters and the out-of-beam neutron spectra measured with Bonner spheres. The simulation results demonstrated that the predicted neutron fluence at the field’s centre is within 8.1% and 2.1% of the gold foil and BC-coated microdosimeter measurements, respectively. The logarithms of the ratios of average simulated to experimental fluences in the thermal (E 0.414 eV), epithermal (0.414 eV < E 11.7 keV) and fast (E 11.7 keV) spectral regions were approximately − 0.03 to + 0.1, − 0.2 to + 0.15, and − 0.4 to + 0.2, respectively. Furthermore, the predicted thermal, epithermal and fast neutron components in-beam at the sample stage position constituted approximately 18%, 64% and 18% of the total neutron fluence. © The Authors - Open Access Open Access This article is licensed under a Creative Commons Attribution 4.0 International.
- ItemNeutron capture enhanced particle therapy: a frontier in hadron therapy(Australian Nuclear Science and Technology Organisation, 2019-09-27) Safavi-Naeini, MNeutron Capture Enhanced Particle Therapy (NCEPT) is a radical new paradigm in radiotherapy being developed by an international team led by ANSTO. NCEPT combines the precision of particle therapy with the cancer-specific targeting capability of neutron capture therapy (NCT). NCEPT magnifies the impact of particle therapy by capturing neutrons - produced internally at the target as a by-product of treatment - inside cancer cells, where they deliver extra dose to the tumour (Fig. 1). NCEPT uses low-toxicity agents containing boron-10 and gadolinium-157 which concentrate in cancer cells, already approved or under development for other medical applications. Simulations and experiments on cancer cells have yielded extremely compelling results, indicating that NCEPT achieves equivalent cancer cell control with between ⅓ and ⅕ of the radiation dose compared to particle therapy alone. NCEPT has generated considerable excitement within the radiation oncology communities in Australia, USA, and in particular in Japan, where it has been dubbed “the future of ion-beam radiotherapy”. Initial discussions regarding the first clinical trials in Japan are currently in progress.
- ItemQuantification of dopamine d2 receptor density and apparent affinity can be used to longitudinally assess transient striatal variations during adolescence using [11c]raclopride pet imaging(John Wiley & Sons, Inc., 2017-04-11) Callaghan, PD; Sobbi, PF; Safavi-Naeini, M; Wimberley, CA; Davis, E; Zahra, D; Arthur, A; Rahardjo, GL; Perkins, G; Pascali, G; Reilhac-Laborde, A; Grégoire, MCBackground Transient increases in striatal dopamine D2 receptors occur during adolescence in rats, correlating with a developmental epoch where synaptic pruning occurs. Alteration of these processes with external stresses during adolescence may lead to affective disorders later in life. Longitudinal PET imaging with [11C]raclopride using a partial saturation design allows assessment of density (Bavail) and affinity changes (appKd) to map neurodevelopmental changes in D2 expression, which necessitates a significant level of receptors occupancy during the PET study. Aims Validate that repeated transient partial saturation of D2 receptors does not bias measures of D2 Bavail and appKd assessed using PET/CT imaging with [11C]raclopride. Methods Three cohorts of male Sprague-Dawley rats (n=6-7/group) underwent a single session of PET/CT imaging (INVEON, Siemens, USA) with [11C]raclopride (5 nmol injected i.v.) as naïve or after repeated partial saturation of D2 receptors: Cohort A received 5nmol raclopride (i.v) weekly from PND35 (postnatal day) to PND96 with PET imaging session at PND96, cohort B was scanned at PND96; Cohort C was scanned at PND35 Datasets were reconstructed (2D-FBP), coregistered with CT and time-activity data extracted using age matched atlas-based volumes of interest (striatum, cerebellum). in vivo receptor density and appKd were derived using kinetic modelling (comparisons used 1-way ANOVA follow by post hoc test). Results Expected differences in Bavail and appKd were seen between the adolescent (PND35) and the adult (PND96) cohorts, corresponding with increases in D2 receptor consistently reported in the literature using post mortem methods. No significant difference was observed in both Bavail and appKd in cohort A, exposed to repeated D2 partial saturation, compared to the naïve cohort B. Conclusion Longitudinal quantification of dopamine D2 receptor density and apparent affinity in vivo using [11C]raclopride PET imaging with partial saturation can be used to map changes in adolescent and adult rats.
- ItemSP-103 - Scandium-47 and lutetium-177 radiolabelling and stability studies of 1st and 2nd generation DOTA-triphenylphosphonium ligands – potential radionuclide theranostics for treatment of glioblastoma multi-forme(Elsevier, 2021-05-17) Wyatt, NA; Hogan, L; Pellegrini, PA; Roberts, MP; Hall, A; Smith, N; Hemzal, E; Hill, L; Howell, NR; Middleton, RJ; Safavi-Naeini, M; Rendina, LM; Fraser, BHScandium-47 has emerged as a promising radioisotope for targeted radionuclide tumor therapy. This is due, to a significant extent, from the combination of low energy / short range β- emission, the availability of a “perfect theranostic pair” with Sc-44 for companion PET imaging, the potential to form highly stable radiometal complexes, and the availability of suitable γ emissions for companion SPECT imaging. Sc-47 also has a shorter half-life (3.35 d) than the chemically similar Lu-177 (6.7 d) which is significant given recent in vitro research that suggests longer lived isotopes require more initial radioactivity to have the same effect upon cell viability [3]. The shorter half-life of Sc-47 also suggests it may be more suitable for smaller biological vectors (with shorter biological half-lives) such as small molecules and low MW peptides. One area of clinical treatment where Sc-47 can have impact and where improvements in patient outcomes and survival rates remain stubbornly low is glioblastoma multiforme (GBM). GBM is the most common and aggressive form of malignant brain tumor and represents around 60% of all adult brain tumors with a global incidence of <10 per 100,000 persons. The prognosis for GBM patients is poor with a -ear survival rate of 37%, 5 year rate of 5% and a median survival time of 10 months. The current standard of treatment is resection of the tumor followed by radiation therapy and chemotherapy. Given this poor prognosis there is a clear and unmet need for improved classes of treatment. Although significant progress has been made towards bringing GBM targeted radionuclide therapies to the clinic, the efforts to date have not included utilizing Sc-44/ Sc-47. Given this we are developing and evaluating Sc-44/Sc-47 and Lu-177/Ga-68 radiolabelled triphenylphosphonium (TPP) functionalised DOTA ligands (1st and 2nd generation) as potential theranostics for GBM. Described herein is our work on comparing the radiolabelling efficiency (Sc-47 vs. Lu-177) and stability studies (PBS pH 7.4, rat plasma) for our 1st and 2nd generation DOTA-TPP ligands. The presence of an additional carbonyl group in the 2nd generation DOTATPP ligand was anticipated to increase the number of donor atoms around the radiometal and affect radiolabelling reaction conditions and, more importantly, increase radiometal complex stability. Copyright © 2021 Elsevier Inc.